PROJECT SUMMARY Congenital heart disease (CHD) affects approximately 1% of all children born per year in the United States. The NHLBI has made significant investments to discover the causes and outcomes of CHD, including research in the Bench-to-Bassinet (B2B) Consortia that spans fundamental discovery science in the Cardiovascular Development Consortium (CvDC), sequencing the genomes of clinically phenotyped children with CHD and their parents in the Pediatric Cardiac Genomics Consortium (PCGC), and long-term clinical follow-up and outcomes research in the Pediatric Heart Network (PHN). The advent of Next Generation Sequencing (NGS) has rapidly accelerated discoveries in cardiovascular development and the genetics and epigenetics of CHD. Both the CvDC and the PCGC have extensive NGS datasets. The CvDC DataHub at the University of Utah currently serves as the programmatic data warehouse and distribution server that organizes NGS datasets and makes them available online. CvDC datasets are complex, containing NGS experiments from seven ?model organism? species (mice, zebrafish, humans, alligator, turtle, chicken, sheep and frogs) and humans. Importantly, the experiments in the CvDC explore the molecular etiology of cardiovascular development through several coordinated -omics approaches, studying changes in the whole-genome transcriptome and in the epigenome (chromatin modifiers, transcription factors, the DNA methylome and higher-order organization of chromatin) during cardiac development and in several mutant genetic backgrounds. The Cardiovascular Development Data Resource Center (CDDRC) will be built on the innovative Mosaic platform to provide a cloud-based collaborative space for organizing, visualizing and understanding genomic data, and for pointing analytic tools to datasets housed anywhere on the cloud. The CDDRC is designed by experts in computational sciences and bioinformatics, in consultation with leaders in the CvDC, PCGC and PHN to be used by non-experts, basic scientists, human geneticists and clinicians. The University of Utah is one of a few institutions in the country that has leadership in all three B2B consortia, reflecting the depth and diversity of our expertise and our commitment to cross-disciplinary collaborations. The CDDRC will provide a suite of cloud-compatible tools and a coordinated and a harmonized set of datasets transported from the previous CvDC DataHub, imported from current CvDC projects, and recruited from the cardiovascular development and pediatric CHD research communities. The CDDRC will facilitate dynamic and investigator- interactive interfaces with multiple -omics datasets from humans and multiple model organisms, resulting in collaborative discoveries of the genetic and epigenetic causes of CHD. In addition, our program will have educational components in Ethical, Legal and Social Implications (ELSI) of CHD genetics and genomics, and an outreach program in CHD computational biology for students from underrepresented groups.